Exhaled nitric oxide as a marker of airway inflammation for an epidemiologic study in schoolchildren.

BACKGROUND Exhaled nitric oxide (eNO) levels are increased in airway inflammatory disorders, such as asthma. OBJECTIVE We sought to determine whether eNO could serve as a noninvasive marker of allergic airway inflammation for an epidemiologic study in schoolchildren. METHODS Two hundred seventy-eight schoolchildren aged 10 to 12 years answered a modified American Thoracic Society questionnaire, and eNO levels and pulmonary function were measured. In 246 subjects serum nonspecific IgE levels and levels of IgE specific to house dust mite, cat, cedar, and mold were also measured. Correlation analysis was used to examine eNO levels, nonspecific IgE levels, antigen-specific IgE levels, and pulmonary function. In addition, we compared these variables between subjects with (recurrent wheezers) and without (nonwheezers) recurrent wheeze. Finally, multiple logistic regression analysis was used to find possible predictors for recurrent wheezers. RESULTS eNO showed significant positive correlations with nonspecific IgE (r=0.62, P <.001) and mite-specific IgE (r=0.74, P <.001) and weak positive correlations with specific IgE to cat and cedar. Only eNO showed a weak but significant inverse correlation with pulmonary function (%FEV(1), P=.035; FEV(1)/forced vital capacity, P=.018). eNO, nonspecific IgE, and mite-specific IgE levels in recurrent wheezers were greater (P <.001), and %FEV(1) was less (P=.06) when compared with values seen in nonwheezers. Finally, eNO was determined by means of multiple logistic regression analysis to be the best predictor for recurrent wheezers compared with other variables (odds ratio, 11.2; 95% CI, 1.33-94.0). CONCLUSION eNO can be used in epidemiologic studies as a noninvasive marker of allergic airway inflammation in schoolchildren.

[1]  P. Barnes,et al.  Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase: effect of inhaled glucocorticoid , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  P. Barnes,et al.  Allergen-induced late asthmatic reactions are associated with elevation of exhaled nitric oxide. , 1995, American journal of respiratory and critical care medicine.

[3]  K. Chung,et al.  Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. , 1998, Thorax.

[4]  Nathan J. Brown,et al.  Exhaled nitric oxide measurements in a population sample of young adults. , 1999, American journal of respiratory and critical care medicine.

[5]  A. Wells,et al.  Increased nitric oxide production in the respiratory tract in asymptomatic pacific islanders: an association with skin prick reactivity to house dust mite. , 2000, The Journal of allergy and clinical immunology.

[6]  P. Barnes,et al.  Exhaled nitric oxide measurements in normal and asthmatic children , 1997, Pediatric pulmonology.

[7]  F. Blasi,et al.  Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing. , 2000, The European respiratory journal.

[8]  L. Boulet,et al.  Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Influence of inhaled corticosteroids. , 2000, American journal of respiratory and critical care medicine.

[9]  J. Stamler,et al.  Expired nitric oxide levels during treatment of acute asthma. , 1995, American journal of respiratory and critical care medicine.

[10]  P. Howarth,et al.  Bronchial mucosal manifestations of atopy: a comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls. , 1992, The European respiratory journal.

[11]  P. J. Barnes,et al.  Increased nitric oxide in exhaled air of asthmatic patients , 1994, The Lancet.

[12]  N. Kissoon,et al.  Measurement of exhaled nitric oxide in children, 2001 , 2002, European Respiratory Journal.

[13]  Y. Nakamura,et al.  Expression of growth factors and remodelling of the airway wall in bronchial asthma. , 1998, Thorax.

[14]  P. Howarth,et al.  Induction of nitric oxide synthase in asthma , 1993, The Lancet.

[15]  M. Ennis,et al.  Bronchoalveolar lavage findings suggest two different forms of childhood asthma , 1997, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[16]  C. Salome,et al.  Toward a definition of asthma for epidemiology. , 1992, The American review of respiratory disease.

[17]  L. Bjermer,et al.  Combined use of exhaled nitric oxide and airway hyperresponsiveness in characterizing asthma in a large population survey. , 2000, The European respiratory journal.

[18]  E. Israel,et al.  Safety and reproducibility of sputum induction in asthmatic subjects in a multicenter study. , 2001, American journal of respiratory and critical care medicine.

[19]  E. Weitzberg,et al.  Exhaled nitric oxide in paediatric asthma and cystic fibrosis. , 1996, Archives of disease in childhood.

[20]  T. Holmen,et al.  Sensitization and exposure to pet allergens in asthmatics versus non-asthmatics with allergic rhinitis. , 2001, Respiratory medicine.

[21]  Anita C. Chalmers,et al.  Airway eosinophilia is associated with wheeze but is uncommon in children with persistent cough and frequent chest colds. , 2001, American journal of respiratory and critical care medicine.

[22]  S. Stick,et al.  A community study of exhaled nitric oxide in healthy children. , 1999, American journal of respiratory and critical care medicine.

[23]  M. Lebowitz,et al.  Changes in the normal maximal expiratory flow-volume curve with growth and aging. , 1983, The American review of respiratory disease.

[24]  B. Brunekreef,et al.  Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children , 2003, Thorax.

[25]  R. Pellegrino,et al.  Airway hyperresponsiveness in asthma: not just a matter of airway inflammation , 1998, Thorax.

[26]  L. Bont,et al.  Airflow limitation during respiratory syncytial virus lower respiratory tract infection predicts recurrent wheezing. , 2001, The Pediatric infectious disease journal.

[27]  R. deShazo.  Bronchoalveolar Lavage in Asthma , 1993 .

[28]  V. Brusasco,et al.  Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. , 1998, American journal of respiratory and critical care medicine.

[29]  C. Sorkness,et al.  Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. , 2003, The Journal of allergy and clinical immunology.

[30]  E. Israel,et al.  Exhaled nitric oxide as a diagnostic test for asthma: online versus offline techniques and effect of flow rate. , 2002, American journal of respiratory and critical care medicine.

[31]  P. Barnes,et al.  Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children , 2003, European Respiratory Journal.

[32]  D. Smith,et al.  Bronchoalveolar lavage in asthma. An update and perspective. , 1993, The American review of respiratory disease.